G Chir. 2016 Mar-Apr;37(2):79-83

Giant endometrial cyst of the liver: a case report and review of the literature.

De Riggi MA, Fusco F, Marino G, Izzo A.

 

Abstract

Endometriosis is a benign condition described as the presence of endometrial- like tissue found outside the uterine cavity. Hepatic endometriosis is one of the rarest localization of extrapelvic endometriosis, only 22 cases have been reported in the literature. The preoperative diagnosis of hepatic endometriosis is rather difficult because in about the half of the patient affected they had no history of endometriosis. Moreover radiological images reveal no characteristic findings for hepatic endometriosis. It is often described as cystic mass with or without solid component, difficult to distinguish from hepatic abscess, hematoma, cystoadenoma or malignant neoplasia. We report a case of a 27-year-old female with a large cystic mass involving the left lobe of the liver. The patient underwent laparoscopic exploration and converted to laparotomy for resection of giant hepatic endometriosis.

 

 

Endocrinology. 2016 Sep;157(9):3332-43.

TGF-β Induces Endometriotic Progression via a Noncanonical, KLF11-Mediated Mechanism.

Correa LF¹, Zheng Y¹, Delaney AA¹, Khan Z¹, Shenoy CC¹, Daftary GS¹.

 

Abstract

Endometriosis, a chronic disease of heterogeneous etiopathology affects 10% of young women and is characterized by ectopic implantation of endometrial cells. Growth and spread of endometriosis lesions involves biological interplay between intrinsic lesion-driven and extrinsic host-responsive mechanisms. We propose a role for TGFβ and its target transcription factor Krüppel-like factor 11 (KLF11) in mediating such mechanisms. Although TGFβ, a pleiotropic cytokine implicated in endometriosis potentially, mediates its pathological phenotypes, KLF11 is associated with endocrine and reproductive tract diseases, specifically progression of endometriosis. In Ishikawa cells, TGFβ1 treatment resulted in noncanonical SMAD-mediated transient up-regulation and sustained repression of KLF11. KLF11 recruits histone deacetylases to epigenetically repress multiple synthetic and metabolic cytochrome P450 (CYP) enzymes such as CYP3A4, which affects endometrial metabolism and pathophysiology. In contrast to KLF11, TGFβ1 treatment caused transient repression and sustained activation of CYP3A4 expression. CYP3A4 increased endometrial cell proliferation and was also increased in human endometriosis lesions compared with eutopic endometrium. To determine whether dysregulation of TGFβ/Klf11/Cyp3a signaling affected endometriotic progression, we treated wild-type control and Klf11-/- mice with a Tgfβ type 1 receptor inhibitor (TGFβR1I) that inhibits Tgfβ signaling upstream of the canonical Smad proteins or a combination of TGFβR1I and a histone acetyltransferase inhibitor that additionally inhibits Klf11 signaling. Disease progression and lesional Cyp3a expression was diminished in TGFβR1I-treated animals and more so in animals treated synergistically with TGFβR1I and histone acetyltransferase inhibitor. TGFβ and KLF11 thus mediate critical, translationally relevant host and lesion-driven responses that enable establishment and progression of endometriosis.

 

 

Gynecol Obstet Invest. 2017;82(4):410-416.

Diagnostic Value of Serial Measurement of C-Reactive Protein in the Detection of a Surgical Complication after Laparoscopic Bowel Resection for Endometriosis.

Riiskjær M¹, Forman A, Kesmodel US, Andersen LM, Ljungmann K, Seyer-Hansen M.

Abstract

AIMS:

The study aimed to assess the diagnostic value of serial monitoring of biochemical inflammatory markers (C-reactive protein (CRP) and white blood cell (WBC) count) in the postoperative diagnosis of anastomotic leakage or ureteral injury after bowel resection for deep infiltrating endometriosis.

METHODS:

This is a review of prospectively collected data from 217 patients who underwent laparoscopic bowel resection for endometriosis from January 2009 to April 2015. Patients with an anastomotic leakage or ureteral injury were identified and classified.

RESULTS:

The frequency of anastomotic leakage requiring reoperation was 8.3%. The frequency of ureteral injury was 4.6%. Median time to diagnosis was 6 days for anastomotic leakage and 8 days for ureteral injury. The daily mean values of serum CRP were significantly higher in patients with a surgical complication starting at the second postoperative day (POD 2, p = 0.004). WBC was significantly higher (p < 0.05) on POD 2 and 3 in patients with a surgical complication. A decrease in CRP from POD 1 to 3 predicted an uncomplicated course in 92.1% of the cases.

CONCLUSION:

A decrease in CRP from POD 1 to 3 was an indicator of uncomplicated subsequent postoperative course. The test is recommended when early discharge after rectal resection for deep infiltrating endometriosis is considered.

 

Gynecol Obstet Invest. 2017;82(3):294-302.

Expression of Angiotensin II Types 1 and 2 Receptors in Endometriotic Lesions.

Nakao T¹, Chishima F, Sugitani M, Tsujimura R, Hayashi C, Yamamoto T.

Abstract

BACKGROUND/AIM:

The aim of this study was to evaluate the gene and protein expression of angiotensin type (AT) 1, AT2 receptors in endometriotic lesions and its relation to prostaglandin (PG) synthases.

MATERIALS AND METHODS:

Endometriosis samples were obtained from 32 patients with endometriotic cysts. Endometrial tissues were obtained during operations for benign gynecological conditions. The expression of the AT1 and AT2 receptor mRNA and that of PG-endoperoxide synthase 2 and microsomal PGE2 synthase-1 (mPGES-1) was examined by quantitative RT-PCR. Immunohistochemical staining was performed for these receptors.

RESULTS:

AT1 and AT2 receptor proteins were mostly located in endometrial glandular epithelium and some stromal cells. Immunoreactivity of the receptor proteins was observed in both the eutopic endometrium and endometriotic lesions. The AT1/AT2 ratio in endometriotic cysts (median 7.29, range 1.88-187.60) was significantly increased compared with that in the eutopic endometrium in the proliferative-phase in controls (median 1.01, range 0.37-2.09, p < 0.001). There was a relationship between the AT1 mRNA expression and that of mPGES-1 mRNA in the endometriotic cysts (r = 0.394089, p < 0.05). There was a significant relationship between the mRNA expression of the AT2 receptor and that of mPGES-1 in eutopic endometrium of non-endometriotic control (r = 0.610714, p < 0.05).

CONCLUSION:

Renin-angiotensin system may play an important role in the pathophysiology of endometriosis.

 

 

Mol Hum Reprod. 2016 Sep;22(9):648-54.

ID2 mediates the transforming growth factor-β1-induced Warburg-like effect seen in the peritoneum of women with endometriosis.

Young VJ¹, Ahmad SF¹, Brown JK¹, Duncan WC¹, Horne AW².

Abstract

STUDY QUESTION:

Is inhibitor of DNA-binding protein 2 (ID2) a mediator of the transforming growth factor (TGF)-β1-induced Warburg-like effect seen in the peritoneum of women with endometriosis?

SUMMARY ANSWER:

The TGF-β1-induced changes in the metabolic phenotype of peritoneal mesothelial cells from women with endometriosis are mediated through the ID2 pathway.

WHAT IS KNOWN ALREADY:

TGF-β1 induces the metabolic conversion of glucose to lactate via aerobic glycolysis (the ‘Warburg effect’) in the peritoneum of women with endometriosis, through increased expression of the transcription factor hypoxia inducible factor α (HIF-1α). ID proteins are transcriptional targets of TGF-β1.

STUDY DESIGN, SAMPLES/MATERIALS, METHODS:

Expression of ID2 was investigated in luteal phase peritoneal biopsies from women with regular menstrual cycles, with and without endometriosis (n = 8-10 each group) by quantitative RT-PCR (qRT-PCR) and immunohistochemistry. ID2 mRNA expression in primary human peritoneal mesothelial cells (HPMC) and immortalized mesothelial cells (MeT-5A) was assessed by qRT-PCR (n = 6). The effects of TGF-β1 and ID2 siRNA on HIF-1α mRNA expression and lactate secretion was assessed using qRT-PCR and a colorimetric lactate assay.

MAIN RESULTS AND THE ROLE OF CHANCE:

ID2 is localized to peritoneal mesothelial and stromal cells of women with and without endometriosis. ID2 mRNA expression is lower in peritoneum adjacent to the endometriosis lesions compared to distal sites (P < 0.01). Exposure of HPMC and MeT-5A cells to physiological concentrations of TGF-β1 decreases ID2 mRNA expression (P < 0.01, P < 0.001, respectively, versus control). ID2 knockdown increases HIF-1α mRNA expression (P < 0.01) and lactate secretion (P < 0.05 versus scrambled control) to the same degree as with exposure to TGF-β1.

LIMITATIONS, REASONS FOR CAUTION:

Primary human cell cultures and a cell line were used in this study, and thus the results may not fully represent the situation in vivo. The results should also be replicated using a larger number of samples.

WIDER IMPLICATIONS OF THE FINDINGS:

Novel therapeutics that target the TGFβ/ID pathway offer a potential role in the treatment of endometriosis.

LARGE SCALE DATA:

None.

STUDY FUNDING AND COMPETING INTERESTS:

This work was funded by a Wellbeing of Women research grant (R42533) awarded to A.W.H., J.K.B. and W.C.D.; and an MRC Centre Grant G1002033. V.J.Y. received grant support from Federation of Women Graduates (134225) and a PhD studentship from the College of Medicine and Veterinary Medicine at the University of Edinburgh. There are no competing interests to declare.

 

 

Mol Cell Endocrinol. 2016 Oct 15;434:210-8.

Lentiviral vector-mediated down-regulation of Notch1 in endometrial stem cells results in proliferation and migration in endometriosis.

He H¹, Liu R¹, Xiong W², Pu D¹, Wang S¹, Li T³.

 

Abstract

The recent characterization of stem/progenitor cells in the endometrium has shed new light for pathogenesis of endometriosis. The present study was undertaken to investigate the role of Notch1, known as a cell fate regulator, in the mechanism of endometriosis. Influence of Notch1 on endometrial stem cells proliferation and migration was evaluated by knocking down Notch1 expression using shRNA. Furthermore, human endometrial stromal and epithelial stem cells with or without LV-Notch1-shRNA were injected into the peritoneal cavity of nude mice, to assess the in vivo effects of a specific antagonist of Notch1 on the progression of endometriosis. The results showed that LV-Notch1-shRNA led to a significant decline of clonogenicity and migration in human endometrial stem cells in vitro, as well as the size of endometriotic lesions in murine models. These data provide evidence that specific inhibition of Notch1 alters endometriotic tissue growth and progression, and may represent a promising potential therapeutic avenue.

 

 

Hum Reprod. 2016 Aug;31(8):1713-22.

Pharmacokinetics, pharmacodynamics, safety and tolerability of an intravaginal ring releasing anastrozole and levonorgestrel in healthy premenopausal women: a Phase 1 randomized controlled trial.

Schultze-Mosgau MH¹, Waellnitz K², Nave R², Klein S³, Kraetzschmar J², Rautenberg T⁴, Schmitz H³, Rohde B².

Abstract

STUDY QUESTION:

What are suitable doses of the aromatase inhibitor anastrozole (ATZ) and the progestin levonorgestrel (LNG), when delivered to the systemic circulation by an intravaginal ring (IVR), for further clinical development as a potential new therapy for the treatment of endometriosis?

SUMMARY ANSWER:

Anticipated targets for pharmacokinetics, pharmacodynamics and safety/tolerability were achieved for both drug components of the IVR at the doses investigated, supporting selection of the doses to be investigated in Phase 2 studies.

WHAT IS KNOWN ALREADY:

Aromatase is a key enzyme in the biosynthesis of estrogens and is known to increase local levels of estradiol (E2) at extragonadal sites. Up-regulation of aromatase expression has been demonstrated in endometriotic lesions and the use of oral aromatase inhibitors has been shown to reduce endometriosis-associated pelvic pain in small-scale clinical trials.

STUDY DESIGN, SIZE, DURATION:

This Phase 1, randomized, multicentre, parallel-group, three-arm, open-label study assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of various IVRs intended for systemic drug delivery. After screening, healthy, ovulating women aged 18-35 years were randomized to use IVRs releasing one of the three ATZ/LNG dose combinations (in vitro nominal daily drug release rates on Day 29: ATZ/LNG 500 µg/20 µg [low dose], ATZ/LNG 1000 µg/30 µg [mid dose] or ATZ/LNG 1500 µg/40 µg [high dose]) for two consecutive 28-day wearing periods without a treatment break.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Sixty women were included in the per protocol set. The primary variables were plasma concentrations of ATZ and LNG at the end of each treatment period and the mean size of largest follicle-like structures (FLSs) over 56 days. Serum concentrations of several hormones were also evaluated, with emphasis on E2 levels.

MAIN RESULTS AND THE ROLE OF CHANCE:

At the end of the first treatment period, geometric mean plasma concentrations of LNG and ATZ, respectively, were 0.228 and 12.5 µg/l for the low dose, 0.269 and 19.8 µg/l for the mid dose and 0.384 and 37.3 µg/l for the high dose; results were similar at the end of the second treatment period. Over the entire treatment period, mean FLS sizes were higher in all three treatment groups than during the pretreatment cycle; more women in the mid- and high-dose groups had FLSs of at least 30 mm (32-45%) than those in the low-dose group (14-24%). Changes in the mean size of FLSs were similar to those reported for low-dose progestin-only oral contraceptives and generally resolved during the 2-month treatment period. Serum E2 levels were decreased, but only one woman in each of the mid- and high-dose groups, and no woman in the low-dose group, had a serum E2 level below 20 pg/ml in both cycles. All ATZ and LNG combinations showed good tolerability.

LIMITATIONS, REASONS FOR CAUTION:

This was an exploratory study; no formal power calculation was performed.

WIDER IMPLICATIONS OF THE FINDINGS:

The results of this first-in-human study of the ATZ/LNG IVR facilitated the selection of ATZ and LNG doses to be investigated in the Phase 2 studies of patients with endometriosis.

STUDY FUNDING/COMPETING INTEREST:

The study was funded by Bayer Pharma AG. T.R. is an employee of DINOX GmbH, which received funding from Bayer Pharma AG to perform this study. M.-H.S.-M., K.W., R.N., S.K., J.K., H.S. and B.R. are or have been employees of Bayer Pharma AG. H.S. is a named inventor on EP 2 552 404 B1, a patent application relating to this work.

 

 

Am J Obstet Gynecol. 2016 Dec;215(6):762.e1-762

Long-term functional outcomes following colorectal resection versus shaving for rectal endometriosis.

Roman H¹, Milles M², Vassilieff M², Resch B², Tuech JJ³, Huet E³, Darwish B², Abo C².

Abstract

BACKGROUND:

Two surgical approaches usually are used in the surgical management of deep infiltrating endometriosis of the rectum: the radical approach that mainly is based on colorectal resection and the conservative or symptom-guided approach that prioritizes conservation of the rectum. There are no data available that compare long-term functional digestive outcomes of 1 approach to the other.

OBJECTIVE:

The purpose of this study was to compare long-term digestive outcomes in women who were treated by either rectal shaving or colorectal resection for deep endometriosis infiltrating the rectum.

STUDY DESIGN:

A retrospective comparative study was performed. All women who were treated with surgery for deep endometriosis infiltrating the rectum by either shaving or colorectal resection at the University Hospital of Rouen from January 2005 to January 2010 were enrolled. Follow-up evaluation was carried out for a minimum of 5 years. Postoperative evaluation of digestive symptoms was performed by 4 standardized gastrointestinal questionnaires: the Gastrointestinal Quality of Life Index, the Knowles-Eccersley-Scott-Symptom score for constipation, the Wexner score for anal continence, and the Bristol Stool Score. Symptoms that were related to endometriosis, fertility, and disease recurrence were obtained from a specific questionnaire.

RESULTS:

A total of 77 women were included. Three women were lost to follow up (3.9%), and 3 were treated by disc excision (3.9%). The mean follow-up time was 80±19 months. Forty-six women underwent conservative rectal shaving, and 25 women underwent colorectal resection. Patient characteristics and the severity of the disease were comparable in both groups. Patients who were treated by rectal shaving had significantly better Gastrointestinal Quality of Life Index values, lower Knowles-Eccersley-Scott-Symptom scores for postoperative constipation, and better anal continence. No statistically significant differences were revealed for postoperative pelvic pain. Rectal recurrence occurred in 8.7% of patients who were treated by conservative surgery: 4.3% underwent secondary colorectal resection and 4.3% were treated secondarily by rectal shaving. Consequently, avoiding a recurrence for merely 1 patient would have required 11 patients to undergo colorectal resection instead of shaving.

CONCLUSION:

Our data suggest that, in patients who are treated for rectal endometriosis, colorectal resection does not improve long-term postoperative functional outcomes when compared with rectal shaving.

 

 

J Minim Invasive Gynecol. 2016 Sep-Oct;23(6):886-92.

Laparoscopic Imaging Techniques in Endometriosis Therapy: A Systematic Review.

Vlek SL¹, Lier MC², Ankersmit M³, Ket JC⁴, Dekker JJ², Mijatovic V², Tuynman JB⁵.

 

Abstract

Endometriosis is a common disease associated with pelvic pain and subfertility. Laparoscopic surgical treatment has proven effective in endometriosis, but is hampered by a high rate of recurrence. The aim of this systematic review was to evaluate the intraoperative identification of endometriosis by enhanced laparoscopic imaging techniques, focusing on sensitivity and specificity. A systematic review was conducted according to PRISMA guidelines in PubMed, Embase, Cochrane Library, and Web of Science. Published prospective studies reporting on enhanced laparoscopic imaging techniques during endometriosis surgery were included. General study characteristics and reported outcomes, including sensitivity and specificity, were extracted. Nine studies were eligible for inclusion. Three techniques were described: 5-ALA fluorescence (5-ALA), autofluorescence (AFI), and narrow-band imaging (NBI). The reported sensitivity of 5-ALA and AFI for identifying endometriosis ranged from 91% to 100%, compared with 48% to 69% for conventional white light laparoscopy (WL). A randomized controlled trial comparing NBI + WL with WL alone reported better sensitivity of NBI (100% vs 79%; p < .001). All 9 studies reported an enhanced detection rate of endometriotic lesions with enhanced imaging techniques. Enhanced imaging techniques are a promising additive for laparoscopic detection and treatment of endometriosis. The 5-ALA, AFI, and NBI intraoperative imaging techniques had a better detection rate for peritoneal endometriosis compared with conventional WL laparoscopy. None of the studies reported clinical data regarding outcomes. Future studies should address long-term results, such as quality of life, recurrence, and need for reoperation.

 

 

Curr Drug Targets. 2017;18(9):997-1002.

Inflammasome as a Key Pathogenic Mechanism in Endometriosis.

Bullon P¹, Navarro JM².

Abstract

BACKGROUND:

Endometriosis remains a challenging condition for clinicians to treat. To improve our results, we have to develop new treatment strategies based on pathophysiological mechanisms targeting the etiologic and pathogenic processes involved.

OBJECTIVES:

Revise new inflammatory pathogenic mechanisms involved in endometriosis, namely inflammasome.

METHOD:

Literature review for the updating of data to give new clues for different options of treatments.

RESULTS:

Inflammasome has been described as a multiprotein complex and is considered a key regulator of the innate and adaptive host response that surveys the cytosol and other compartments into the cell. It is involved in the immediate detection and responds to the presence of danger- and pathogen-associated molecular patterns named DAMPs and PAMPs respectively, and has been described in several cells, mainly on immune cells of the myeloid lineage and epithelial cells in tissues with mucosal surfaces. Four inflammasome are formed in a stimulus-dependent manner of distinct composition. They are the Noll Like Receptors (NLR) proteins Nlrp1b, Nlrp3, Nlrc4, and Nlrp6, as well as the absent in melanoma 2 (AIM2). They activate the production of IL-1β and IL-18 that induce a host response such as pyroptosis, a proinflammatory cell death and the secretion of leaderless cytokines and growth factors. Inflammasome is linked to atherosclerosis, periodic fever syndromes, vitiligo, Crohn’s disease, gout, asbestosis, silicosis, Alzheimer’s disease and periodontitis. Endometriosis has been related with IL-1β and Another NLR, Nlrp7, was correlated with myometrial invasion in human endometrial cancer tissue.

CONCLUSIONS:

These new clues regarding the pathogenic mechanisms involving the inflammasome may be crucial in the future development for endometriosis therapy.

 

Int J Mol Sci. 2016 Jul 7;17(7).

Endometriosis Might Be Inversely Associated with Developing Chronic Kidney Disease: A Population-Based Cohort Study in Taiwan.

Huang BS^1,2, Chang WH^3,4, Wang KC⁵, Huang N⁶, Guo CY⁷, Chou YJ⁸, Huang HY⁹, Chen TJ¹⁰, Lee WL^11,12, Wang PH.

 

Abstract

This study was conducted to determine the risk of chronic kidney disease (CKD) among women with endometriosisin Taiwan. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan. A total of 27,973 women with a diagnosis of endometriosis and 27,973 multivariable-matched controls (1:1) from 2000 to 2010 were selected. Cox regression and computed hazard ratios (HR) with 95% confidence intervals (95% CI) were used to determine the risk of CKD among women with endometriosis. The incidence rates (IR, per 10,000 person-years) of CKD among women with and without endometriosis were 4.64 and 7.01, respectively, with a significantly decreased risk of CKD (crude HR 0.65, 95% CI 0.53-0.81; adjusted HR 0.69, 95% CI 0.56-0.86) among women with endometriosis. The IR of CKD progressively increased with age, but the trend of lower CKD risk among women with endometriosis was consistent. However, the lower risk of CKD in women with endometriosis was no longer statistically significant after adjusting for menopausal status (adjusted HR 0.85, 95% CI 0.65-1.10). The results suggest that endometriosis is inversely associated with CKD, but this effect was mediated by menopause. The possible mechanism of this association is worthy of further evaluation.

 

 

J Ethnopharmacol. 2016 Dec 24;194:386-394.

Wenshen Xiaozheng Tang induces apoptosis and inhibits migration of ectopic endometriotic stromal cells.

Zhang Z¹, Cheng X², Gui T³, Tao J⁴, Huang M⁵, Zhu L⁶, Luo M⁷, Cao P⁸, Wan G⁹.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Wenshen Xiaozheng Tang (WXT), a traditional Chinese medicine prescription, exerted a good therapeutic effect on endometriosis. However, the underlying mechanism is unclear. In the present study, we sought to evaluate the effect of WXT on the proliferation and migration of ectopic endometriotic stromal cells and explore the potential molecular mechanism.

MATERIALS AND METHODS:

Primary stromal cells derived from ectopic endometriotic lesions of patients with endometriosis were isolated and cultured. The inhibition effect of WXT on cell proliferation was determined by MTT. Apoptosis of ectopic endometriotic cells treated with WXT was analyzed with Annexin V-FITC/7-AAD staining. The activation of caspases was detected by western blot analysis. The influence of WXT on migration of ectopic endometriotic cells was measured by scratch wound healing assay and Transwell assay. The DNA binding activity of NF-κB and the expression of nuclear p65 protein were determined by electrophoretic mobility shift assay and western blot analysis, respectively. The impact of WXT on the expression of NF-κB regulated gene products involved in apoptosis and migration was determined by western blot analysis.

RESULTS:

WXT inhibited the proliferation of ectopic endometriotic cells in a time- and dose-dependent manner. In addition, WXT treatment resulted in significant induction of apoptosis through the activation of caspases and inhibition of migration in ectopic endometriotic cells. WXT notably suppressed constitutive NF-κB-DNA-binding activity as well as TNF-α induced nuclear translocation of NF-κB p65 subunit in ectopic endometriotic cells. Moreover, WXT diminished the expression of NF-κB regulated gene products involved in apoptosis and migration, including c-IAP1, c-IAP2, XIAP, survivin, Mcl-1, COX-2 and MMP-9.

CONCLUSIONS:

Our results indicate that WXT induces apoptosis and inhibits migration of ectopic endometriotic stromal cells.

 

 

Reproduction. 2016 Oct;152(4):283-91.

l-Carnitine affects preimplantation embryo development toward infertility in mice.

Kyvelidou C¹, Sotiriou D¹, Antonopoulou T¹, Tsagkaraki M², Tserevelakis GJ³, Filippidis G³, Athanassakis I⁴.

 

Abstract

l-Carnitine (l-Cn), despite the beneficial role as energy-generating substance delivering long-chain fatty acids to the β-oxidation pathway in mitochondria, has been accused to cause an endometriosis-like state to BALB/c mice manifested by increased inflammatory cytokines in serum and peritoneal fluid, accumulation of immune cells in the peritoneal cavity and uterine walls and most importantly, correlating to infertility. Exploring this type of infertility, the effect of l-Cn on preimplantation embryo development, ovarian integrity and systemic maternal immunity was studied. Using nonlinear microscopy analysis, which was shown to be a powerful tool for determining embryo quality by quantitatively estimating the lipid body (LB) content of the cells, it was shown that in vitro and in vivo administration of l-Cn significantly decreased LB mean area in zygotes. Daily intraperitoneal administration of 2.5mg l-Cn for 3, 4 and 7days to mice significantly decreased the percent of normal zygotes. However, only the 7-day treatment persisted by affecting 2- and 8-cell stage embryos, while almost abolishing blastocyst development. Such effects were accompanied by abnormal ovarian histology, showing increased numbers of corpora luteus and elevated progesterone concentration in the serum. In addition, it was shown that the 7-day l-Cn treatment pushed maternal systemic immunity toward inflammation and immunosuppression by increasing CD11b-, CD25- and CD11bGr1-positive cells in spleen, which opposed the necessity for immunostimulation at these early stages of pregnancy. In conclusion, the results presented here demonstrated that elevated doses of l-Cn affect early stages of embryo development, leading to infertility.

 

 

Case Rep Gastroenterol. 2016 May 19;10(1):115-20.

Benign Cystic Mesothelioma Misdiagnosed as Peritoneal Carcinomatosis.

Shin HD¹, Kim SB¹.

 

Abstract

Benign cystic mesothelioma (BCM) is a rare benign disease that forms multicystic masses in the abdomen, pelvis, and retroperitoneum. It occurs predominantly in young to middle-aged women. The majority of cases were associated with a history of abdominal or pelvic operation, a history of endometriosis, and pelvic inflammatory disease. We present a unique case of BCM which is different to the previous cases. The patient was a 52-year-old man showing features of peritoneal carcinomatosis accompanied by ascites on abdominal computed tomography scans. We herein report a case of BCM misdiagnosed with peritoneal carcinomatosis.

 

 

Ned Tijdschr Geneeskd. 2016;160(0):A9883.

Thoracic endometriosis with aspecific manifestation.

Hamel CC¹, de Kruif JH, Jansen JP, Barendregt WB.

Abstract

BACKGROUND:

Endometriosis is a common disease, especially in subfertile women. The most common location is in the pelvis, but extragenital locations are also possible. This far less common condition has been described in almost all tissues in the body. Symptoms occurring cyclically are characteristic of endometriosis.

CASE DESCRIPTION:

A 37-year-old woman was discovered by chance to have ascites and pleural effusion. She had no symptoms of this. Thoracoscopy showed an image consistent with thoracic endometriosis. After initial drug therapy was unsuccessful, surgical intervention was performed.

CONCLUSION:

Thoracic endometriosis is a rare disease, in which the cyclical nature of the symptoms often leads to correct diagnosis. Drug therapy is the preferred treatment for patients.

 

 

Cochrane Database Syst Rev. 2016 Jul 13;7

Combination of the non-invasive tests for the diagnosis of endometriosis.

Nisenblat V¹, Prentice L, Bossuyt PM, Farquhar C, Hull ML, Johnson N.

Abstract

BACKGROUND:

About 10% of women of reproductive age suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive tests available in clinical practice to accurately diagnose endometriosis. This review assessed the diagnostic accuracy of combinations of different non-invasive testing modalities for endometriosis and provided a summary of all the reviews in the non-invasive tests for endometriosis series.

OBJECTIVES:

To estimate the diagnostic accuracy of any combination of non-invasive tests for the diagnosis of pelvic endometriosis (peritoneal and/or ovarian or deep infiltrating) compared to surgical diagnosis as a reference standard. The combined tests were evaluated as replacement tests for diagnostic surgery and triage tests to assist decision-making to undertake diagnostic surgery for endometriosis.

SEARCH METHODS:

We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as the following databases to April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.

SELECTION CRITERIA:

We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of women of reproductive age suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of a combination of several testing modalities with the findings of surgical visualisation of endometriotic lesions.

DATA COLLECTION AND ANALYSIS:

Three review authors independently collected and performed a quality assessment of the data from each study by using the QUADAS-2 tool. For each test, the data were classified as positive or negative for the surgical detection of endometriosis and sensitivity and specificity estimates were calculated. The bivariate model was planned to obtain pooled estimates of sensitivity and specificity whenever sufficient data were available. The predetermined criteria for a clinically useful test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of 0.95 and above and a specificity of 0.50 and above, which ‘rules out’ the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of 0.50 and above and a specificity of 0.95 and above, which ‘rules in’ the diagnosis with high accuracy if there is a positive result (SpIN test).

MAIN RESULTS:

Eleven eligible studies included 1339 participants. All the studies were of poor methodological quality. Seven studies evaluated pelvic endometriosis, one study considered DIE and/or ovarian endometrioma, two studies differentiated endometrioma from other ovarian cysts and one study addressed mapping DIE at specific anatomical sites. Fifteen different diagnostic combinations were assessed, including blood, urinary or endometrial biomarkers, transvaginal ultrasound (TVUS) and clinical history or examination. We did not pool estimates of sensitivity and specificity, as each study analysed independent combinations of the non-invasive tests.Tests that met the criteria for a replacement test were: a combination of serum IL-6 (cut-off >15.4 pg/ml) and endometrial PGP 9.5 for pelvic endometriosis (sensitivity 1.00 (95% confidence interval (CI) 0.91 to 1.00), specificity 0.93 (95% CI, 0.80, 0.98) and the combination of vaginal examination and transvaginal ultrasound (TVUS) for rectal endometriosis (sensitivity 0.96 (95% CI 0.86 to 0.99), specificity 0.98 (95% CI 0.94 to 1.00)). Tests that met the criteria for SpIN triage tests for pelvic endometriosis were: 1. a multiplication of urine vitamin-D-binding protein (VDBP) and serum CA-125 (cut-off >2755) (sensitivity 0.74 (95% CI 0.60 to 0.84), specificity 0.97 (95% CI 0.86 to 1.00)) and 2. a combination of history (length of menses), serum CA-125 (cut-off >35 U/ml) and endometrial leukocytes (sensitivity 0.61 (95% CI 0.54 to 0.69), specificity 0.95 (95% CI 0.91 to 0.98)). For endometrioma, the following combinations qualified as SpIN test: 1. TVUS and either serum CA-125 (cut-off ≥25 U/ml) or CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.79 (95% CI 0.64 to 0.91), specificity 0.97 (95% CI 0.91 to 1.00)); 2. TVUS and serum CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.54 (95% CI 0.37 to 0.70), specificity 0.97 (95% CI 0.91 to 1.0)); 3-4. TVUS and serum CA-125 (cut-off ≥20 U/ml or cut-off ≥25 U/ml) (sensitivity 0.69 (95% CI 0.49 to 0.85), specificity 0.96 (95% CI 0.88 to 0.99)); 5. TVUS and serum CA-125 (cut-off ≥35 U/ml) (sensitivity 0.52 (95% CI 0.33 to 0.71), specificity 0.97 (95% CI 0.90 to 1.00)). A combination of vaginal examination and TVUS reached the threshold for a SpIN test for obliterated pouch of Douglas (sensitivity 0.87 (95% CI 0.69 to 0.96), specificity 0.98 (95% CI 0.95 to 1.00)), vaginal wall endometriosis (sensitivity 0.82 (95% CI 0.60 to 0.95), specificity 0.99 (95% CI 0.97 to 1.0)) and rectovaginal septum endometriosis (sensitivity 0.88 (95% CI 0.47 to 1.00), specificity 0.99 (95% CI 0.96 to 1.00)).All the tests were evaluated in individual studies and displayed wide CIs. Due to the heterogeneity and high risk of bias of the included studies, the clinical utility of the studied combination diagnostic tests for endometriosis remains unclear.

AUTHORS’ CONCLUSIONS:

None of the biomarkers evaluated in this review could be evaluated in a meaningful way and there was insufficient or poor-quality evidence. Laparoscopy remains the gold standard for the diagnosis of endometriosis and using any non-invasive tests should only be undertaken in a research setting.

 

 

Hum Reprod. 2016 Sep;31(9):1981-6.

Dienogest mediates midkine suppression in endometriosis.

Nirgianakis K¹, Grandi G², McKinnon B³, Bersinger N³, Cagnacci A², Mueller M³.

Abstract

STUDY QUESTION:

What are the effects of dienogest (DNG) on midkine (MK) production in women with endometriosis?

SUMMARY ANSWER:

DNG-mediated down-regulation of MK in vivo and in vitro.

WHAT IS KNOWN ALREADY:

DNG is an oral progestin that alleviates painful symptoms of women with endometriosis with a favourable tolerability and safety profile. Its effects on MK, a growth factor that plays an important role in endometriosis, have not yet been investigated.

STUDY DESIGN, SIZE, DURATION:

Prospective in vivo study on 283 patients subjected to laparoscopy for benign pathologies in a University hospital and in vitro cultures of primary endometrial stromal cells (ESC) from 6 of these women with histologically confirmed endometriosis.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

MK concentrations in the peritoneal fluid (PF) of women were measured by ELISA and compared based on endometriosis status and the use of DNG. A subsequent in vitro analysis with ESC was used to confirm the direct influence of DNG and other progestins including, norethisterone acetate (NETA) and medroxyprogesterone acetate (MPA) on MK mRNA production.

MAIN RESULTS AND THE ROLE OF CHANCE:

The final study population consisted of 253 women. Of these, 165 suffered from endometriosis, with 62 of them taking DNG (DNG group) and 103 taking no hormone treatment (non-DNG group) during at least 3 months before surgery. Another 88 women were endometriosis free (non-endometriosis group). The concentration of MK was highest in the PF of women in the non-DNG group (median 5.26 ng/ml, IQR 2.74-8.46). Significantly lower concentrations were found in the non-endometriosis group (median 3.51 ng/ml, IQR: 1.90-7.53, P = 0.028). The lowest concentrations were found in the DNG group (median 2.44 ng/ml, IQR: 1.12-4.70, P < 0.0001 versus non-DNG group, P = 0.048 versus non-endometriosis group). The treatment of primary cultured ESC with DNG (10(-5) M) suppressed MK mRNA production (P = 0.016), whereas MPA (P = 0.109) and NETA (P = 0.422) at same concentrations did not show a similar effect.

LIMITATIONS, REASONS FOR CAUTION:

The non-randomized design of the study.

WIDER IMPLICATIONS OF THE FINDINGS:

These findings could indicate a direct effect of DNG on endometriotic cells that could contribute to its effectiveness in the treatment of this disease.

STUDY FUNDING/COMPETING INTERESTS:

Funding was received from Swiss National Science Foundation (Grant No. 320030_140774). M.D.M. has received fees for speaking at scientific meetings from Bayer. The other authors have no conflicts of interest to declare.The authors state that the manufacturer of dienogest has in no way influenced the performance or outcomes of this study.

 

 

Hum Reprod. 2016 Sep;31(9):2072-81.

Young women’s psychological distress after a diagnosis of polycystic ovary syndrome or endometriosis.

Rowlands IJ¹, Teede H², Lucke J³, Dobson AJ⁴, Mishra GD⁴.

Abstract

STUDY QUESTION:

Do young women with polycystic ovary syndrome (PCOS) or endometriosis report more psychological distress than their peers without a history of these conditions?

SUMMARY ANSWER:

Young women (aged 18-23 years) with PCOS or endometriosis had a greater risk of moderate to severe psychological distress than women without a history of these conditions.

WHAT IS KNOWN ALREADY:

Psychological distress appears common among women with PCOS and endometriosis. However, population-based studies that examine the psychological outcomes for adolescents and young women are generally absent from the literature.

STUDY DESIGN, SIZE, DURATION:

This is a secondary analysis of data collected from 17 015 young, Australian women participating in a national, longitudinal cohort study. Women were first surveyed in 2012-2013 when they were aged 18-23 years. In 2014, women completed the second survey when they were aged 19-24 years and 11324 (67%) women responded.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

We analysed data from 11 238 women who participated in both Surveys 1 and 2 and who responded to questions about PCOS and endometriosis. Using logistic regression, we compared the odds of moderate to severe psychological distress at Surveys 1 and 2 for women reporting a recent diagnosis (within the last 12 months) of PCOS or endometriosis and women with a pre-existing diagnosis, with that for women without a history of these conditions.

MAIN RESULTS AND THE ROLE OF CHANCE:

At Survey 2, around 60% of women reporting a diagnosis of PCOS or endometriosis had moderate to severe levels of psychological distress. Compared to women without a history of these conditions, the odds of moderate to severe psychological distress at Survey 2 were significantly higher for women recently diagnosed with PCOS [Adjusted Odds Ratio (AOR) = 1.62, 95% CI = 1.21-2.18] or endometriosis(AOR= 1.77; 95% CI = 1.20-2.63) and for women with a pre-existing diagnosis of PCOS (AOR = 1.57, 95% CI = 1.30-1.89) or endometriosis (AOR = 1.61; 95% CI = 1.26-2.06). Women recently diagnosed with PCOS or endometriosis also had a greater likelihood of moderate to severe distress in the year prior to their diagnosis. The association between PCOS and psychological distress was attenuated when adjusting for BMI, but hormonal contraceptive use did not attenuate the risk of distress among the women with PCOS or endometriosis.

LIMITATIONS, REASONS FOR CAUTION:

All data were self-reported and, therefore, the diagnoses of PCOS or endometriosis were not confirmed by a medical practitioner.

WIDER IMPLICATIONS OF THE FINDINGS:

Health professionals should be aware of the potential psychosocial and healthcare needs among young women with these conditions, particularly women with PCOS who are obese. While hormonal contraceptives may help to regulate the hormonal aspects of these conditions, they do not appear to reduce women’s psychological distress. Because psychological distress among the young women in this study remained elevated even after diagnosis, this supports the need for multidisciplinary health care to help women adjust to their diagnosis and treatment regimens and facilitate positive, long-term mental health outcomes. Future research that examines medical and psychosocial sources of distress for young women with PCOS and endometriosis is needed.

STUDY FUNDING/COMPETING INTERESTS:

I.J.R. was supported by an Australian National Health and Medical Research Council Centre for Research Excellence (grant number: APP1000986). G.D.M. is funded by the Australian Research Council Future Fellowship (FT120100812). The Australian Longitudinal Study on Women’s Health is funded by the Australian Government Department of Health. H.T. is supported by an Australian National Health and Medical Research Council Practitioner Fellowship. The authors declare that no competing interests exist.

 

 

Reprod Toxicol. 2016 Oct;65:87-94.

Association of prenatal and early life exposure to tetrachloroethylene (PCE) with polycystic ovary syndrome and other reproductive disorders in the cape cod health study: A retrospective cohort study.

Mahalingaiah S¹, Winter MR², Aschengrau A³.

Abstract

BACKGROUND:

Tetrachloroethylene (PCE) is an organic lipophilic solvent with possible neuroendocrine toxicity. The objective of this study was to determine the association of prenatal and early childhood exposure to PCE-contaminated drinking water and development of adult-onset Polycystic Ovary Syndrome (PCOS), endometriosis, difficulty conceiving and miscarriage.

METHODS:

Five-hundred exposed and 331 unexposed female participants born between 1969 and 1983 completed questionnaires on demographic and lifestyle characteristics, and reproductive disorders. Residential locations from the prenatal period through five years of age were used to estimate early life PCE exposure with water modeling software.

RESULTS:

For any early life exposure to PCE, the adjusted risk ratio for PCOS was 0.9 (95% CI: 0.5-1.6). No statistically significant associations were observed for increasing levels of exposure with PCOS or the other reproductive disorders.

CONCLUSION:

No meaningful associations were found among adult women with early life exposure to PCE-contaminated drinking water and adult-onset reproductive disorders.

 

 

Reprod Sci. 2016 Oct;23(10):1359-70.

Analysis of Serum microRNA Profile by Solexa Sequencing in Women With Endometriosis.

Wang L¹, Huang W², Ren C¹, Zhao M³, Jiang X⁴, Fang X⁵, Xia X⁶.

Abstract

OBJECTIVES:

The potential roles of serum microRNAs (miRNAs), as biomarkers, in noninvasive diagnosis of endometriosis have been reported by microarray analysis. However, microarray analysis cannot perform well in outcome accuracy and repeatability and is not suitable to be used for exploring new targets. Here, Solexa sequencing, a wide and precise method, was adopted to further analyze the serum miRNAs profile in endometriosis, which may offer more evidence to apply serum miRNAs as biomarkers in diagnosis of endometriosis.

MATERIALS AND METHODS:

Serum samples were collected from 30 patients with minimal-mild endometriosisand 20 women without endometriosis as control. Expression of serum miRNAs was measured by Solexa sequencing and validated by quantitative real-time polymerase chain reaction (qPCR).

RESULTS:

Solexa sequencing showed 93.63% clean readouts for all small RNAs in the serum of patients with endometriosis and controls. A total of 108 miRNAs were found to be differentially expressed in the serum of patients with endometriosis by deep sequencing, compared to controls. Among them, 98 miRNAs were significantly downregulated, while 10 miRNAs were significantly upregulated. Only 21 of 98 significantly downregulated miRNAs, and none of significantly upregulated miRNAs were reported in published literatures, which may be due to the differences in samples and analytical methods. The Solexa sequencing results were consequently validated by qPCR in additional samples. Some miRNAs were identified to be promising diagnostic markers of endometriosis. The functional annotation of target genes revealed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that a majority of differential miRNAs might be involved in endometriosis.

CONCLUSION:

Circulating miRNAs may be useful as detection biomarkers for the early diagnosis of minimal-mild endometriosis.

 

 

Reprod Sci. 2017 Mar;24(3):445-455.

Decidualization Differentially Regulates microRNA Expression in Eutopic and Ectopic Endometrial Stromal Cells.

Aoyagi Y¹, Nasu K^1,2, Kai K¹, Hirakawa T¹, Okamoto M¹, Kawano Y¹, Abe W^1,3, Tsukamoto Y⁴, Moriyama M⁴, Narahara H¹.

 

Abstract

Decidualization of the endometrium and endometriosis involves the morphological and biochemical reprogramming of the estrogen-primed proliferative stromal compartment under the continuing influence of progesterone. Here, we evaluated the involvement of microRNA in the decidualization processes of normal endometrial stromal cells (NESCs) and endometriotic cyst stromal cells (ECSCs). In vitro decidualization of NESCs and ECSCs was induced by long-term culture with a combination of 0.5 mmol/L of dibutyryl cyclic adenosine monophosphate and 100 nmol/L of dienogest. We investigated the effect of in vitro decidualization on the microRNA and messenger RNA (mRNA) expression profiles of the NESCs and ECSCs using global microarray techniques and an Ingenuity Pathways Analysis. Decidualization differentially enhanced the miR-30a-5p expression in the NESCs and the miR-210 expression in the ECSCs. The enhanced miR-30a-5p expression in the NESCs correlated with the increased mRNA expression of Krüppel-like factor 9 and period circadian clock 3 as well as the decreased mRNA expression of tolloid-like 1, tolloid-like 2, and paired-like homeodomain 1. The enhanced expression of miR-210 in the ECSCs correlated with the decreased mRNA expression of growth hormone receptor and thymidine kinase 1. Although there is no direct evidence, we speculate that the loss of miR-30a-5p-mediated mechanisms of decidualization and the acquisition of miR-210-mediated mechanisms of decidualization may be involved in the progesterone resistance in endometriosis. Further investigations are necessary to test this speculation.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:14-24

Nerve fibers and endometriotic lesions: partners in crime in inflicting pains in women with endometriosis.

Yan D¹, Liu X², Guo SW³.

 

Abstract

One of major objectives in treating endometriosis is to alleviate pain since dysmenorrhea and other types of pain top the list of complaints from women with endometriosis who seek medical attention. Indeed, endometriosis-associated pain (EAP) is the most debilitating of the disease that negatively impacts on the quality of life in affected women, contributing significantly to the burden of disease and adding to the substantial personal and societal costs. Unfortunately, the mechanisms underlying the EAP are still poorly understood. In the last two decades, one active research field in endometriosis is the investigation on the distribution and genesis of nerve fibers in eutopic and ectopic endometrium, and the attempt to use endometrial nerve fiber density for diagnostic purpose. Since EAP presumably starts with the terminal sensory nerves, in or around endometriotic lesions, that transduce noxious mediators to the central nervous system (CNS) which ultimately perceives pain, this field of research holds the promise to elucidate the molecular mechanisms underlying the EAP, thus opening new avenues for novel diagnostics and therapeutics. In this review, we shall first briefly provide some basic facts on nerve fibers, and then provide an overview of some major findings in this filed while also note some conflicting results and expose areas in need of further research. We point out that since recently accumulated evidence suggests that endometriotic lesions are wounds undergoing repeated tissue injury and repair, the relationship between endometriotic lesions and nerve fibers is not simply unidirectional, i.e. lesions promote hyperinnervations. Rather, it is bidirectional, i.e. endometriotic lesions and nerve fibers engage active cross-talks, resulting in the development of endometriosisand pain. That is, nerve fibers and endometriotic lesions are actually partners in crime in inflicting pains in women with endometriosis, aided and abetted possibly by other culprits, some yet to be identified. We provide a list of possible perpetrators likely to be involved in this crime. Finally, we discuss possible implications when viewing the relationship from this vista.

 

 

Reprod Toxicol. 2017 Mar;68:59-71

Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models.

Bruner-Tran KL¹, Gnecco J², Ding T², Glore DR², Pensabene V², Osteen KG³.

 

Abstract

Humans and other animals are exposed to a wide array of man-made toxicants, many of which act as endocrine disruptors that exhibit differential effects across the lifespan. In humans, while the impact of adult exposure is known for some compounds, the potential consequences of developmental exposure to endocrine disrupting chemicals (EDCs) is more difficult to ascertain. Animal studies have revealed that exposure to EDCs prior to puberty can lead to adult reproductive disease and dysfunction. Specifically, in adult female mice with an early life exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we demonstrated a transgenerational occurrence of several reproductive diseases that have been linked to endometriosis in women. Herein, we review the evidence for TCDD-associated development of adult reproductive disease as well as known epigenetic alterations associated with TCDD and/or endometriosis. We will also introduce new “Organ-on-Chip” models which, combined with our established murine model, are expected to further enhance our ability to examine alterations in gene-environment interactions that lead to heritable disease.

 

 

Fertil Steril. 2016 Sep 15;106(4):959-66.

Endocrine disrupting chemicals and endometriosis.

Smarr MM¹, Kannan K², Buck Louis GM³.

 

Abstract

Endometriosis is an estrogen dependent gynecologic disease with lasting implications for many women’s fertility, somatic health, and overall quality of life. Growing evidence suggests that endocrine disrupting chemicals (EDCs) may be etiologically involved in the development and severity of disease. We weigh the available human evidence focusing on EDCs and endometriosis, restricting to research that has individually quantified chemical concentrations for women, included a comparison group of unaffected women, and used multivariable analytic techniques. Evidence supporting an environmental etiology for endometriosis includes metals/trace elements, dioxins, and other persistent organic pollutants, as well as nonpersistent chemicals, such as benzophenones and phthalates. To address the equivocal findings for various EDCs, future research directions for filling data gaps include [1] use of integrated clinical and population sampling frameworks allowing for incorporation of new diagnostic modalities; [2] the collection of various biologic media, including target tissues for quantifying exposures; [3] study designs that offer various comparison groups to assess potentially shared etiologies with other gynecologic disorders; and [4] novel laboratory and statistical approaches that fully explore all measured EDCs for the assessment of mixtures and low dose effects and the use of directed acyclic graphs and supporting causal analysis for empirically delineating relationships between EDCs and endometriosis.

 

 

J Reprod Med. 2016 May-Jun;61(5-6):249-53.

Scar Endometrioma: An Uncommon Yet Easily Treated Condition.

Ozturk A, Kaya C, Bozkurtoglu H, Tan N, Yananli ZD, Ucmakli E.

Abstract

OBJECTIVE:

To illustrate and emphasize the need for keeping scar endometrioma in mind in order to facilitate an early diagnosis in cases of a mass detected on the abdominal wall in women who have undergone a cesarean section.

STUDY DESIGN:

Records of 21 patients were reviewed retrospectively. All the patients complained of a mass on the abdominal wall and had undergone cesarean section in the past. Endometrioma was confirmed histopathologically for each patient. Information about the characteristics of the patients are retrieved from the patient records and analyzed.

RESULTS:

The average age of patients was 31 years. The average duration before onset of the complaints in the postcesarean section period was 32.9 months, and the average duration of the complaints was 25.3 months. In most cases (62%) the scar endometrioma was located at the right end of the Pfannenstiel incision. The average size of the endometrioma masses was 30 mm. Recurrence was not observed in any of the patients during an average follow-up of 31.3 months after total excision.

CONCLUSION:

Scar endometrioma is a rare disease which can be treated easily. If a mass on a cesarean section scar which becomes sensitive during menstruation is detected in a patient with history of cesarean section, the diagnosis of scar endometrioma should be suspected.

 

 

Eur Rev Med Pharmacol Sci. 2016 Jul;20(13):2769-72.

Differential studies of ovarian endometriosis cells from endometrium or oviduct.

Liu W¹, Wang HY.

Abstract

OBJECTIVE:

To study the prominent differences between endometriosis (EMT) cells derived from ovary, oviduct and endometrium, and to provided new ideas about the pathogenesis of endometriosis.

PATIENTS AND METHODS:

From June 2010 to June 2015, 210 patients diagnosed with endometriosis were enrolled in our study. Patients were treated by laparoscopy or conventional surgeries in our hospital. Ovarian chocolate cyst and paired normal ovarian tissues, fimbriated extremity of fallopian and uterine cavity endomembrane tissues were collected, prepared and observed by microscope. PCR was used for amplification of target genes (FMO3 and HOXA9) and Western blot was used to evaluate FMO3 and HOXA9 expression levels.

RESULTS:

In 95 cases, endometriosis cells were derived from oviduct epithelial. In 110 cases, endometriosis cells were derived from the endometrium, and in 5 cases it was derived from the ovary itself. FMO3 gene transcription and protein expression were higher in oviduct cells while HOXA9 gene transcription and protein expression were higher in endometrial cells. In 89 cases the endometriosis cells were derived from oviduct epithelial and in 113 cases endometriosis cells were derived from the endometrium. Protein levels indicated that endometriosis cells in 85 cases were derived from oviduct epithelial and in 116 cases were derived from the endometrium.

CONCLUSIONS:

A large number of ovarian endometriosis cells were derived from oviduct epithelial.

 

 

Arch Toxicol. 2017 Jan;91(1):97-107.

Vitamin D and chronic diseases: the current state of the art.

Muscogiuri G¹, Altieri B², Annweiler C^3,4, Balercia G⁵, Pal HB⁶, Boucher BJ⁷, Cannell JJ⁸, Foresta C⁹, Grübler MR^10,11, Kotsa K¹², Mascitelli L¹³, März W^14,15,16, Orio F^17,18, Pilz S^11,19, Tirabassi G⁵, Colao A²⁰.

 

Abstract

The objective was to provide the current state of the art regarding the role of vitamin D in chronic diseases (osteoporosis, cancer, cardiovascular diseases, dementia, autism, type 1 and type 2 diabetes mellitus, male and female fertility). The document was drawn up by panelists that provided their contribution according to their own scientific expertise. Each scientific expert supplied a first draft manuscript on a specific aspect of the document’s topic that was subjected to voting by all experts as “yes” (agreement with the content and/or wording) or “no” (disagreement). The adopted rule was that statements supported by ≥75 % of votes would be immediately accepted, while those with <25 % would be rejected outright. Others would be subjected to further discussion and subsequent voting, where ≥67 % support or, in an eventual third round, a majority of ≥50 % would be needed. This document finds that the current evidence support a role for vitamin D in bone health but not in other health conditions. However, subjects with vitamin D deficiency have been found to be at high risk of developing chronic diseases. Therefore, although at the present time there is not sufficient evidence to recommend vitamin D supplementation as treatment of chronic diseases, the treatment of vitamin D deficiency should be desiderable in order to reduce the risk of developing chronic diseases.

 

 

 

 

BJOG. 2016 Jul 18.

Maternal and neonatal outcomes in women with colorectal endometriosis.

Thomin A^1,2, Belghiti J^1,2, David C³, Marty O^1,2, Bornes M^1,2, Ballester M^1,2,4, Roman H^5,6, Daraï E^1,2,4.

Abstract

OBJECTIVE:

To evaluate delivery and neonatal outcomes in women with resected or in situ bowel endometriosis.

DESIGN:

Retrospective cohort study.

SETTING:

France.

POPULATION AND SAMPLE:

Analysis of 72 pregnancies from 67 women followed for colorectal endometriosisfrom 2001 to 2014 in six centres including two university expert centres for endometriosis.

METHODS:

Univariate analysis of maternal and neonatal outcomes.

MAIN OUTCOME MEASURES:

Routes for delivery and rate of complications.

RESULTS:

The colorectal surgery group comprised 41 women and the in situ colorectal group, 26 women. Overall, half of the women underwent caesarean section. A high incidence of postoperative complications (39%) was observed after caesarean section with no difference between the groups. Surgical difficulties at newborn extraction (22%) and postoperative complications (39%) occurred more often in women with anterior deep infiltrating endometriosis (respectively 63 versus 11%, P = 0.007 and 67% versus 26%, P = 0.046) independently of prior surgery for endometriosis. In the remaining half, vaginal delivery required an operative procedure in 28% of the women with a significant increase in postpartum complications compared with those who did not require a procedure (P = 0.001). Overall, the incidence of postpartum complications was lower after vaginal delivery (14%) than after caesarean section (39%) (P = 0.03).

CONCLUSION:

Pregnant women with colorectal endometriosis, irrespective of prior surgery, should be informed of the high risk of delivery by caesarean section. Vaginal delivery is preferrable in this setting because of the lower incidence of postpartum complications.

TWEETABLE ABSTRACT:

Due to the incidence of postpartum complications whatever the route of delivery, women should receive level III maternal care.

 

 

Curr Opin Rheumatol. 2016 Sep;28(5):497-505.

Environmental exposures and the development of systemic lupus erythematosus.

Barbhaiya M¹, Costenbader KH.

Abstract

PURPOSE OF REVIEW:

This review examines evidence relating environmental factors to the development of systemic lupus erythematosus (SLE).

RECENT FINDINGS:

The strongest epidemiologic evidence exists for the associations of silica, cigarette smoking, oral contraceptives, postmenopausal hormone therapy and endometriosis, with SLE incidence. Recent studies have also provided robust evidence of the association between alcohol consumption and decreased SLE risk. There are preliminary, conflicting or unsubstantiated data that other factors, including air pollution, ultraviolet light, infections, vaccinations, solvents, pesticides and heavy metals such as mercury, are related to SLE risk. Biologic mechanisms linking environmental exposures and SLE risk include increased oxidative stress, systemic inflammation and inflammatory cytokine upregulation, and hormonal triggers, as well as epigenetic modifications resulting from exposure that could lead to SLE.

SUMMARY:

Identifying the environmental risk factors related to risk of SLE is essential as it will lead to increased understanding of pathogenesis of this complex disease and will also make risk factor modification possible for those at increased risk.

 

 

Gynecol Oncol. 2016 Oct;143(1):87-92.

Endometriosis and risks for ovarian, endometrial and breast cancers: A nationwide cohort study.

Mogensen JB¹, Kjær SK², Mellemkjær L¹, Jensen A³.

Abstract

OBJECTIVE:

A growing body of evidence suggests that endometriosis increases the risk for ovarian cancer, but it is less well studied whether the excess risk is confined to certain histotypes. Furthermore, it is not fully resolved if endometriosis is associated with endometrial- and breast cancer. The aim was to study overall- and histotype-specific risks for these hormone-dependent cancers in women with endometriosis.

METHODS:

In the Danish National Patient Register, we identified 45,790 women with a clinical diagnosis of endometriosis during 1977-2012. We linked the cohort to the Danish Cancer Register and calculated standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs).

RESULTS:

Endometriosis was associated with increased risks for ovarian cancer (SIR 1.34; 95% CI: 1.16-1.55), due primarily to endometrioid (SIR 1.64; 95% CI: 1.09-2.37) and clear-cell types (SIR 3.64; 95% CI: 2.36-5.38). An excess risk was also observed for endometrial cancer (SIR 1.43; 95% CI: 1.13-1.79), primarily of type 1 (SIR 1.54; 95% CI: 1.20-1.96); and the risk for breast cancer was increased among women aged ≥50years at first diagnosis of endometriosis (SIR 1.27; 95% CI: 1.12-1.42).

CONCLUSIONS:

The results corroborate previous findings of increased risks for endometrioid and clear-cell ovarian cancer in women with endometriosis. As the first cohort study to date, we observed a significantly increased risk for endometrial cancer in women with a diagnosis of endometriosis. The increased breast cancer risk among women with endometriosis diagnosed at ≥50years of age should be studied further.

 

 

Gynecol Endocrinol. 2016 Sep;32(9):741-744.

The impact of unilateral salpingectomy on antral follicle count and ovarian response in ICSI cycles: comparison of contralateral side.

Demir B¹, Bozdag G², Sengul O³, Kahyaoglu I¹, Mumusoglu S², Zengin D².

Abstract

OBJECTIVE:

To determine the impact of salpingectomy on the ovarian reserve. Comparisons are made with the contralateral side in patients with unilateral salpingectomy undergoing intracytoplasmic sperm injection (ICSI) cycles.

STUDY DESIGN:

Patients under 40 with unilateral salpingectomy and without history of ovarian surgery were selected for the multicentre retrospective study. Women with bilateral salpingectomy and history of endometriosiswere excluded from the study. Antral follicle count, controlled ovarian hyperstimulation (COH) parameters and number of collected oocytes were the main outcome measures of the study.

RESULTS:

A total of 56 patients were eligible for this study. The mean age of the patients was 31.6 ± 4.7 years. The reasons for the salpingectomy were hydrosalpinx (39.3%, n = 22) and ruptured ectopic pregnancy (60.7%, n = 34). The ongoing pregnancy rate per embryo transfer was 30.6%. There was no statistically significant difference between the operated and non-operated sides in antral follicle count (AFC), follicles  ≥ 17 mm and 10-17 mm on day of human chorionic gonadotrophin (hCG), or number of aspirated oocytes. In the subgroup analysis, AFC, number of growing follicles on day of hCG and number of collected oocytes were comparable between the ectopic pregnancy group and hydrosalpinx group.

CONCLUSION:

The study suggests that salpingectomy is not associated with detrimental effects on AFC and ovarian response.

 

 

Am J Reprod Immunol. 2016 Sep;76(3):193-8.

Neutrophil depletion reduces endometriotic lesion formation in mice.

Takamura M¹, Koga K¹, Izumi G¹, Urata Y¹, Nagai M¹, Hasegawa A¹, Harada M¹, Hirata T¹, Hirota Y¹, Wada-Hiraike O¹, Fujii T¹, Osuga Y¹.

Abstract

PROBLEM:

Neutrophils are known to be accumulated in endometriosis; however, direct evidence of the impact of neutrophils in the development of endometriosis was lacking. To clarify the importance of neutrophils, we examined the effect of neutrophil depletion on the development of endometriosis.

METHOD OF STUDY:

Ovariectomized, estradiol-replaced, 8-week-old, female BALB/c mice were injected with endometrial fragments (Day 0). Neutrophils were depleted by anti-Gr-1 antibody, either in the early stage (from Day 1 to Day 3, group E) or late stage (from Day 8 to Day 12, group L). Control mice (group C) did not receive antibodies. On Day 14, mice were killed and the number and weight of endometriotic lesions were counted and weighed.

RESULTS:

The number of endometriotic lesions was significantly less in group E in comparison with Group C and Group L. Weight per lesion did not differ between groups.

CONCLUSION:

Neutrophils are essential for the initial formation of endometriosis.

 

 

Int J Surg Case Rep. 2016;26:24-6.

A rare case of ileus caused by ileum endometriosis.

Bratu D¹, Chicea R², Ciprian T³, Beli L¹, Dan S¹, Mihetiu A¹, Adrian B⁴.

Abstract

INTRODUCTION:

We report our experience involving a rare case of ileum endometriosis complicated with small bowel obstruction.

PRESENTATION OF CASE:

33 years old female patient, admitted to emergency service with abdominal pain, abdominal distension, and vomiting. Abdominal X-ray showed dilated small bowel loops. Computerized tomography scan showed dilated small intestine segments excepting last ileum loop, gastric distension, enlarged ovaries. Emergency laparotomy was performed, showing acute bowel obstruction due to a stenotic tumor placed on the terminal ileum, cecum tumors, multiple tumors in Douglas pouch, multiple mesenteric enlarged lymph nodes. Right colectomy is performed with an ileo-transverso stomy placed in right hypochondrium. Postoperative evolution without complication, patient discharged after 13-days hospitalization. After hormonal treatment, she returned for a second look and ileotransverso anastomosis.

DISCUSSION:

Gastrointestinal involvement of endometriosis has been found in 3%-37% of menstruating women. Ileum localization is very rare (1%-7%), causing intestinal obstruction 7%-23% of cases. Intraoperative differential diagnosis is difficult, predisposing at confusion with other types of tumors. In the absence of fast microscopic exam, the tumor was considered malignant and imposed a right hemicolectomy.

CONCLUSION:

Intestinal obstruction due to ileum endometriosis is a rare condition, however, it should always be considered in the differential diagnosis in women of reproductive age.

 

 

 

Int J Fertil Steril. 2016 Jul-Sep;10(2):261-3.

An Introduction to The Royan Human Ovarian Tissue Bank.

Abtahi NS¹, Ebrahimi B¹, Fathi R¹, Khodaverdi S², Mehdizadeh Kashi A², Valojerdi MR³.

 

Abstract

From December 2000 until 2010, the researchers at Royan Institute conducted a wide range of investigations on ovarian tissue cryopreservation with the intent to provide fertility pres- ervation to cancer patients that were considered to be candidates for these services. In 2010, Royan Institute established the Royan Human Ovarian Tissue Bank as a subgroup of the Embryology Department. Since its inception, approximately 180 patients between the ages of 747 years have undergone consultations. Ovarian samples were cryopreserved from 47 patients (age: 7-35 years) diagnosed with cervical adenocarcinoma (n=9); breast carcinoma (n=7), Ewing’s sarcoma (n=7), opposite side ovarian tumor (n=7), endometrial adenocarci- noma (n=4), malignant colon tumors (n=3), as well as Hodgkin’s lymphoma, major thalas- semia and acute lymphoblastic leukemia (n=1-2 patients for each disease). Additionally, two patients requested ovarian tissue transplantation after completion of their treatments.

 

 

Int J Surg Case Rep. 2016;26:30-3.

Rare manifestation of endometriosis causing complete recto-sigmoid obstruction: A case report.

Arafat S¹, Alsabek MB², Almousa F³, Kubtan MA⁴.

Abstract

INTODUCTION:

Endometriosis is a disease in which endometrial epithelium implanted outside the uterus. Although the endometrial tissue can implant anywhere, the most common places are the ovary and pelvic peritoneum. We present a rare case of recto-sigmoid endometriosis that causes a complete large bowel obstruction in a non-reproductive age woman who came with no specific symptoms of endometriosis and the diagnosis was made after surgical resection.

CASE PRESENTATION:

A 50 years old female who never been married and admitted to have no sexual experience in her life, presented with symptoms of acute bowel obstruction. She underwent sigmoid colectomy as the primary diagnosis was colonic tumor, but the histopathological reports showed the diagnosis with recto-sigmoidal Endometriosis. At the second laparotomy for closure of colostomy, the uterus was abnormal and she had a hysterectomy with salpingio-oopherectomy to prevent recurrence. The histopathological report revealed cervical, ovarian, and fallopian tube endometriosis.

DISCUSSION:

Unlike our patient, most patients complain of the common symptoms of endometriosis such as dysmenorrhea, dyspareunia, and dyschezia and many of them came with infertility as a main complaint which make them undergo further investigations like laparoscopy, and lead to pre-surgical diagnosis of endometriosis. But in case of complete bowel obstruction, urgent laparotomy is the treatment of choice.

CONCLUSION:

Although Intestinal endometriosis is rare to cause bowel obstruction physicians and surgeons should always consider it as a differential diagnosis of bowel obstruction even without specific symptoms, to prevent surgery in incomplete obstruction.

 

 

Am J Obstet Gynecol. 2016 Dec;215(6):760.e1-760.e14.

Multifactorial contributors to the severity of chronic pelvic pain in women.

Yosef A¹, Allaire C², Williams C², Ahmed AG³, Al-Hussaini T³, Abdellah MS³, Wong F², Lisonkova S², Yong PJ⁴.

Abstract

BACKGROUND:

Chronic pelvic pain affects ∼15% of women, and is associated with significant societal cost and impact on women’s health. Identifying factors involved in chronic pelvic pain is challenging due to its multifactorial nature and confounding between potential factors. For example, while some women with endometriosis have chronic pelvic pain, there may be comorbid conditions that are implicated in the chronic pelvic pain rather than the endometriosis itself.

OBJECTIVE:

We sought to explore multifactorial variables independently associated with the severity of chronic pelvic pain in women.

STUDY DESIGN:

We used baseline cross-sectional data from an ongoing prospective cohort, collected from patient online questionnaires, physical examination, and physician review of medical records. Participants were recruited from a tertiary referral center for endometriosis and chronic pelvic pain in Vancouver, British Columbia, Canada, from December 2013 through April 2015. Exclusion criteria included menopausal status or age >50 years. Primary outcome was self-reported severity of chronic pelvic pain in the last 3 months (0-10 numeric rating scale). Potential associated factors ranged from known pain conditions assessed by standard diagnostic criteria, validated psychological questionnaires, musculoskeletal physical exam findings, as well as pain-related, reproductive, medical/surgical, familial, demographic, and behavioral characteristics. Mann-Whitney, Kruskal-Wallis, or Spearman test were used to identify variables with an association with the primary outcome (P < .05), followed by multivariable linear regression to control for confounding and to identify independent associations with the primary outcome (P < .05).

RESULTS:

Overall, 656 women were included (87% consent rate), of whom 55% were diagnosed with endometriosis. The following factors were independently associated with higher severity of chronic pelvic pain: abdominal wall pain (P = .005), pelvic floor tenderness (P = .004), painful bladder syndrome (P = .019), higher score on Pain Catastrophizing Scale (P < .001), adult sexual assault (P = .043), higher body mass index (P = .023), current smoking (P = .049), and family history of chronic pain (P = .038). Severity of chronic pelvic pain was similar between women with and without endometriosis.

CONCLUSION:

Multifactorial variables independently associated with severity of chronic pelvic pain were identified, ranging from myofascial/musculoskeletal, urological, family history, and psycho-social factors. Continued research is required to validate these factors and to determine whether any are potentially modifiable for the management of chronic pelvic pain.

 

 

Reprod Sci. 2017 Mar;24(3):382-392.

Effect of Lignocaine on IL-6, IL-8, and MCP-1 in Peritoneal Macrophages and Endometriotic Stromal Cells.

Wickström K¹, Stavréus-Evers A², Vercauteren O², Olovsson M², Edelstam G^2,3.

Abstract

OBJECTIVE:

The objective was to evaluate the effect of lignocaine on cytokine expression and secretion in vitro in peritoneal fluid macrophages and endometriotic stromal cells.

DESIGN:

Experimental in vitro study on human cells.

POPULATION AND SAMPLE:

Peritoneal fluid (n = 10) and samples from endometriotic cysts (n = 7) were collected from 13 women (women with endometriosis n = 8, and healthy controls n = 5) during surgery for clinical reasons.

METHODS:

Macrophages from the peritoneal fluid and cells from the inside of the endometriotic cysts capsules were isolated and cultivated for 24 to 48 hours in medium with and without the supplement of lignocaine 0.1 or 1.0 mg/mL. Relative gene expression of monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and IL-8 was evaluated with quantitative polymerase chain reaction and compared between treated and untreated cells with Wilcoxon matched pairs. The concentrations of MCP-1, IL-6, and IL-8 were measured using enzyme-linked immunosorbent assay and were compared between treated and untreated cells with Wilcoxon matched pairs.

RESULTS:

The gene expression and protein secretion of IL-8 in endometriotic stromal cells after incubation with lignocaine 0.1 mg/mL were significantly decreased after 24 hours compared to the controls ( P = .028 and P = .018). Macrophages from healthy controls had a significant lower gene expression of all tested cytokines ( P = .043) after treatment with lignocaine, but there were no significant differences in protein level. Macrophages from women with endometriosis showed diverging results since 3 of 5 samples showed increased gene expression of 1 (n = 2) or 2 cytokines (n = 1) after lignocaine treatment.

CONCLUSION:

Lignocaine can affect the gene expression and secretion of some proinflammatory cytokines in vitro.

 

 

Surg Endosc. 2017 Mar;31(3):1487.

Segmental left colectomy: a modified caudal-to-cranial approach.

Milone M¹, Milone F².

Abstract

BACKGROUND:

We have designed a modified caudal-to-cranial approach to perform laparoscopic left colectomy preserving the inferior mesenteric artery for benign colorectal diseases.

METHODS:

IRB approval and informed consent have been obtained. A dissection is conducted to separate the descending mesocolon of the Gerota’s plan from the medial aspect to the peritoneal lining to the left parietal gutter. The peritoneal layer is incised parallel to the vessel and close to the colonic wall. The dissection is continued anteriorly up to reach the resected parietal gutter. A passage into the mesentery of the upper rectum is created for the allocation of the stapler and the dissection of the rectum. These maneuvers permit to straighten the mesentery simplifying the identification and cutting of the sigmoid arteries. A caudal-to-cranial dissection of the mesentery is performed from the sectioned rectum to the proximal descending colon by a sealed envelope device. It can be very useful to mobilize the colon in any direction: laterally, medially, or upward. The dissection is performed along the course of the vessel up to the proximal colon, with progressive sectioning of the sigmoid arterial branches. The specimen is extracted by a pfannenstiel incision. The anastomosis is performed transanally with a circular stapler according to Knight-Griffin technique.

RESULTS:

We performed a laparoscopic segmental colectomy using this approach for 21 patients with benign sigmoid lesions: 13 diverticulitis, 3 flat polypoid lesions (no lift-up sign), and 5 bowel endometriosis. The mean operative time and blood loss were 161.4 ± 15.7 min and 50 ± 40 ml, respectively. There were not a single conversion to open surgery and no any leakage or stricture. Only 2 cases of intraluminal bleeding and 1 case of wound infection (treated conservatively) were observed.

CONCLUSION:

We consider this approach to be safe and useful for segmental colectomy to be performed sectioning the sigmoid artery close to the colonic wall.

 

 

Fertil Steril. 2016 Oct;106(5):1129-1135

Complications during pregnancy and delivery in women with untreated rectovaginal deep infiltrating endometriosis.

Exacoustos C¹, Lauriola I², Lazzeri L³, De Felice G³, Zupi E⁴.

Abstract

OBJECTIVE:

To study outcomes and complications during pregnancy and at delivery in women with a posterior deep infiltrating endometriosis (DIE) nodule persisting after surgery and diagnosed at transvaginal sonography (TVS) in comparison with a control group of women without endometriosis.

DESIGN:

Multicenter observational and cohort study.

SETTING:

University hospital.

PATIENT(S):

Women (n = 200) with a posterior DIE nodule equal or more than 2 cm centimeters in size who desired a pregnancy and a control group of women (n = 300) with no previous recorded diagnosis of endometriosiswho delivered in our clinic during the same time period.

INTERVENTION(S):

Patient data collected from medical charts and by phone interviews.

MAIN OUTCOME MEASURE(S):

Evaluation of complications during pregnancy and delivery.

RESULT(S):

Of the 101 women with a posterior DIE nodule, 52 become pregnant among whom 25 used assisted reproductive technology. Of these 52 pregnancies, 11 ended in an early abortion, and 41 delivered a baby; 13 (31.7%) had a premature delivery, 7 (17.8%) a placenta praevia, and 28 (68.2%) had a cesarean delivery. When compared with the control group, the women with endometriosis had a higher risk of pregnancy complicated by preterm birth, placenta previa, placental abruption, and hypertension. Cesarean delivery and complications during surgery (hysterectomy, hemoperitoneum, and bladder injuries) were statistically significantly more frequent in women with endometriosis than in controls.

CONCLUSION(S):

Women with an incomplete removal of posterior DIE have a high complications rate during pregnancy and delivery.

 

 

Gynecol Endocrinol. 2017 Jan;33(1):70-74.

Risk factors and biomarkers for the recurrence of ovarian endometrioma: about the immunoreactivity of progesterone receptor isoform B and nuclear factor kappa B.

Han AR^1,2, Lee TH², Kim S³, Lee HY³.

 

Abstract

Ovarian endometrioma is one of the important causes of poor ovarian reserve and up to half of them have been recurred. However, the treatment for recurrence prevention has limited efficiency and repeated surgery makes worsen the ovarian reserve. To find better management for recurrence prevention, we investigated risk factors and biomarkers for the recurrent endometriomas. The medical records of women with history of surgical dissection for ovarian endometrioma were collected. After exclusion of the cases with concurrent hysterectomy, been menopaused during follow-up, incomplete medical record, and loss of follow-up, a total of 134 women were enrolled. Immunohistochemical staining for progesterone receptor isoform B (PR-B) and nuclear factor kappa B (NFκB) was done with the fixed tissue blocks of their endometriomas which were collected at the time of surgery. Severity of dysmenorrhea and co-existence of adenomyosis had significant correlation with recurrence of endometrioma. Serum CA-125 level at the time of recurrence was higher than the highest level of CA-125 during follow-up in non-recurred group (55.6 versus 21.3 U/mL, p = 0.014). Increased PR-B (p = 0.041) and decreased NFκB (p = 0.036) immunoreactivity were found in recurrent group. However, to determine the possibility of immunoreactivity of PR-B and NFκB as biomarkers for recurrent endometrioma, further studies of various races and large numbers with prospective design are needed.

 

 

Nat Commun. 2016 Jul 25;7:12350.

Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis.

Steinthorsdottir V¹, Thorleifsson G¹, Aradottir K², Feenstra B³, Sigurdsson A¹, Stefansdottir L¹, Kristinsdottir AM¹, Zink F¹, Halldorsson GH¹, Munk Nielsen N³, Geller F³, Melbye M^3,4,5, Gudbjartsson DF^1,6, Geirsson RT², Thorsteinsdottir U^1,7, Stefansson K^1,7.

 

Abstract

We conducted a genome-wide association scan (GWAS) of endometriosis using 25.5 million sequence variants detected through whole-genome sequencing (WGS) of 8,453 Icelanders and imputed into 1,840 cases and 129,016 control women, followed by testing of associated variants in Danish samples. Here we report the discovery of a new endometriosis susceptibility locus on 4q12 (rs17773813[G], OR=1.28; P=3.8 × 10(-11)), upstream of KDR encoding vascular endothelial growth factor receptor 2 (VEGFR2). The variant correlates with disease severity (P=0.0046) when moderate/severe endometriosis cases are tested against minimal/mild cases. We further report association of rs519664[T] in TTC39B on 9p22 with endometriosis (P=4.8 × 10(-10); OR=1.29). The involvement of KDR in endometriosis risk highlights the importance of the VEGF pathway in the pathogenesis of the disease.

 

 

J Med Life. 2016 Apr-Jun;9(2):180-2.

Focal adenomyosis (intramural endometriotic cyst) in a very young patient – differential diagnosis with uterine fibromatosis.

Manta L¹, Suciu N¹, Constantin A¹, Toader O¹, Popa F².

 

Abstract

Introduction. Adenomyosis is a widespread disease usually affecting the late reproductive years of the women’s life, which has a great impact on their fertility. The most common form is diffuse adenomyosis, while focal adenomyosis, a cystic variant, is very rare, particularly in patients younger than 30 years old. Materials and methods. We reported a rare case of a 20-year-old Caucasian woman with cystic adenomyosis who was admitted in our service with severe chronic pelvic pain, dysmenorrhea, and menorrhagia, who had received conservative surgical treatment to preserve fertility and improve her obstetrical prognosis. Results and Discussions. Although the necrobiosis of a uterine fibroid was suspected preoperatively, the extemporaneous histopathological exam revealed adenomyosis associated with fibroleiomyoma with hyaline dystrophy and multiple foci of endometriosis of cystic formation in the wall of a young woman without any risk factors. Conclusion. Although a rare lesion in young patients, cystic adenomyosis should be considered when chronic pelvic pain is exacerbated during menstruation and is associated with a uterine tumor. In young patients, the differential diagnosis should be made with uterine malformations (hematometra), necrobiosis of uterine fibroids, pelvic endometriosis. The surgical treatment should be conservative with the excision of the lesion, always taking into account fertility preservation in young patients.

 

 

Med J Islam Repub Iran. 2016 Apr 10;30:352.

Can combination of hysterosalpingography and ultrasound replace hysteroscopy in diagnosis of uterine malformations in infertile women?

Vahdat M¹, Sariri E², Kashanian M³, Najmi Z⁴, Mobasseri A⁵, Marashi M⁶, Mohabbatian B⁷, Ariana S⁸, Moradi Y⁹.

Abstract

BACKGROUND:

Müllerian anomalies are associated with infertility. Hysteroscopy as the gold standard for evaluating Müllerian anomalies is an invasive, expensive and risky procedure which requires enough experience. Transvaginal sonography (TVS) and hysterosalpingography (HSG) are less invasive procedures, but there is little known about the accuracy of these tests. The aim of this study was to evaluate the accuracy of the combination of TVS and HSG with hysteroscopy as the gold standard.

METHODS:

Medical records of infertile women who were undertaken all three diagnostic modalities were reviewed to analyze their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

RESULTS:

Ninety-nine infertile women were assessed with a mean±SD age of 29.1±6.47 years, mean±SD duration of themarriage of 8.9±10.28 years, and mean±SD duration of infertility of 5.6± 4.16 years. The sensitivity, specificity, PPV, and NPV of TVS were 98.55%, 30%, 76.4%, and 90%, respectively. HSG had a sensitivity of 95.6%, specificity of 60%, PPV of 84.62%, and NPV of 85.71%.When both modalities were combined, the sensitivity, specificity, PPV, and NPV were 94.2, 66.67, 86.67, and 83.33%, respectively. The diagnostic accuracy of single TVS, HSG or combined techniques was statistically similar that was equal to 77.7, 84.8 and 85.8 % respectively.

CONCLUSION:

The accuracy of combination of two diagnostic modalities, 2D TVS and HSG is not higher than HSG alone for assessing uterine malformation in infertile women.

 

 

J Matern Fetal Neonatal Med. 2017 Jun;30(12):1434-1436

Neonatal uterine bleeding as a biomarker for reproductive disorders during adolescence: a worldwide call for systematic registration by nurse midwife.

Puttemans P^1,2, Benagiano G³, Gargett C⁴, Romero R⁵, Guo SW⁶, Brosens I¹.

 

Abstract

Neonatal uterine bleeding (NUB) occurs in approximately 5% of newborns and is generally considered to be of little clinical significance. However, the real clinical importance of this condition and its long-term implications remain to be determined. The reason why NUB is rare despite high circulating levels of progesterone can be attributed to a progesterone resistance present in a majority of neonates. Recent work indicates that NUB represents a significant biomarker for events that can occur later-on during adolescence. Indeed, clinical studies have shown that “neonatal menstruation” constitutes a sign of fetal distress during late pregnancy, reflecting a stage of endometrium development that may subsequently have an impact on the reproductive life of the adolescent and the young adult. Via retrograde flow, NUB can cause endometrial stem/progenitor cells to arrive into the pelvic cavity and survive there, dormant underneath the peritoneal surface, until menarche activates them. Indeed, there is both clinical and epidemiological evidence of a link between NUB and adolescent endometriosis. In addition, if progesterone resistance persists till the onset of menarche, in case of an early teen pregnancy, it can result in a disorder of deep placentation. Therefore, we propose that NUB should be carefully recorded so that prospective studies can examine its links with reproductive disorders in adolescence and beyond.

 

 

Ceska Gynekol. 2016 Apr;81(2):140-6.

Use of methotrexate in the ectopic pregnancy and pregnancy of unknown location.

Racková J, Driák D, Neumannová H, Hurt K, Sehnal B, Halaška M.

Abstract

OBJECTIVE:

There are only a few gynaecological departments in the Czech Republic that use medical treatment of the ectopic pregnancy (EP) or persistent pregnancy of unknown location (PUL). We have started using this method in 2008 at our clinic. The aim of this study was to assess the success rate of conservative medical treatment with methotrexate (MTX) in the dose of 1 mg/kg intramuscularly in patients with ectopic pregnancy or persistent pregnancy of unknown location and to compare the results of clinical history, clinical finding and laboratory results in a group of successful and a group of unsuccessful treatment.

TYPE OF STUDY:

Retrospective analysis.

SETTING:

Charles University in Prague, 1st Medical Faculty and Hospital Bulovka, Department of Obstetrics and Gynaecology, Prague.

METHODS:

Patients diagnosed with EP or persistent PUL diagnosed at the outpatient of our clinic in 01/2008 – 08/2014 who were hemodynamically stable and fulfilled the indication for medical treatment were enrolled in the study. Treatment success was decrease of free subunit of β-hCG (β-hCG) < 5 IU/L independent of the number of methotrexate doses administered.

RESULTS:

Two hundred and eleven patients were diagnosed with EP or PUL, sixty-three were eligible for our study and fulfilled the criteria for methotrexate treatment, fifty six women were finally analysed. From this number forty eight (86%) had clinically and laboratory diagnosed EP and eight (14%) were diagnosed with persistent PUL. Forty one patients (73%) had a successfull treatment (Group I) with the β-hCG level decrease <5 IU/L in a mean time of 27 days. When comparing the data of successful and unsuccessful treatment (Group II) we found a difference in the non-significant initial β-hCG level. In Group I there was a median β-hCG 538 IU/L (100-3852 IU/l), whereas in the unsuccessful Group II it was 1100 IU/L (300-3240 IU/l). Group I included more nuliparous women and more women with clinical histories of EP. Group II included more heavy smokers. The mean hematosalpinx diameter for group II, measured by transvaginal ultrasound, was larger. There were also more patients with endometriosis or deep infiltrating endometriosis in Group II, subsequently verified during laparoscopy, compared to Group I. There was no tubal rupture in these patients.

CONCLUSION:

The results of our study are comparable with foreign literature publications. We consider the pharmacological treatment of ectopic preganancy or persistent pregnancy of unknown location as effective and relatively safe for patients, with similar impact on a woman’s fertility as laparoscopic salpingectomy.

 

 

Am J Public Health. 2016 Sep;106(9):1669-76.

Contributions of the Nurses’ Health Studies to Reproductive Health Research.

Chavarro JE¹, Rich-Edwards JW¹, Gaskins AJ¹, Farland LV¹, Terry KL¹, Zhang C¹, Missmer SA¹.

Abstract

OBJECTIVES:

To review the Nurses’ Health Study’s (NHS’s) contribution to identifying risk factors and long-term health consequences of reproductive events.

METHODS:

We performed a narrative review of the NHS I, NHS II, NHS3, and Growing Up Today Study (GUTS) publications between 1976 and 2016.

RESULTS:

Collection of detailed reproductive history to identify breast cancer risk factors allowed the NHS to document an association between menstrual irregularities, a proxy for polycystic ovary syndrome (PCOS), and increased risk of diabetes and cardiovascular disease. The NHS II found that infertility associated with ovulation problems and gestational diabetes are largely preventable through diet and lifestyle modification. It also identified developmental and nutritional risk factors for pregnancy loss, endometriosis, and uterine leiomyomata. As women in NHS II age, it has become possible to address questions regarding long-term health consequences of pregnancy complications and benign gynecologic conditions on chronic disease risk. Furthermore, the NHS3 and GUTS are allowing new lines of research into human fertility, PCOS, and transgenerational effects of environmental exposures.

CONCLUSIONS:

The multigenerational resources of the NHSs and GUTS, including linkages of related individuals across cohorts, can improve women’s health from preconception through late adulthood and onto the next generation.